Olcegepant hydrochloride (C09-1160-129)

Olcegepant hydrochloride (BIBN-4096 hydrochloride) is a potent and selective non-peptide antagonist of the calcitonin gene-related peptide 1 (CGRP1) receptor with IC 50 of 0.03 nM and with a K i of 14.4 pM for human CGRPIn VitroOlcegepant possesses higher affinity for the human CGRP receptor than the endogenous ligand CGRP and 150-fold higher affinity compared to the peptidic antagonist CGRP8-37. Olcegepant reverses CGRP-mediated vasodilation in human cerebral vessels and inhibits neurogenic vasodilation in a surrogate animal model of migraine pathophysiology. Olcegepant (BIBN4096BS) is extremely potent at primate CGRP receptors exhibiting an affinity (K i ) for human CGRP receptors of 14.4±6.3 (n=4) pM. Several lines of evidence suggest that a calcitonin-gene related peptide (CGRP) receptor antagonist may serve as a novel abortive migraine treatment. Olcegepant (BIBN4096BS) exhibits competitive antagonism at the CGRP receptor present in SK-N-MC cells. Isolated human cerebral, coronary, and omental arteries are studied with a sensitive myograph technique. CGRP induces a concentration-dependent relaxation that is antagonized by Olcegepant in a competitive manner. MCE has not independently confirmed the accuracy of these methods. They are for reference only.In VivoOlcegepant (BIBN4096BS) in doses between 1 and 30 μg/kg (i.v.) inhibits the effects of CGRP, released by stimulation of the trigeminal ganglion, on facial blood flow in marmoset monkeys. Pre-treatment with Olcegepant (900 μg/kg) inhibits the capsaicin-induced expression of Fos throughout the spinal trigeminal nucleus by 57%. In contrast, the expression of phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion is not changed by Olcegepant pre-treatment. Olcegepant (0.3 to 0.9 mg/kg, i.v.) markedly reduces mechanical allodynia in CCI-ION rats. Olcegepant (0.6 mg/kg, i.v.) significantly reduces the number of c-Fos immunolabeled cells in spinal nucleus of the trigeminal nerve and upregulation of ATF3 transcript (a marker of neuron injury) but not that of interleukin-6 in trigeminal ganglion of CCI-ION rats. MCE has not independently confirmed the accuracy of these methods. They are for reference only.Form:SolidIC50& Target:IC50: 0.03 nM (CGRP1), Ki: 14.4 pM (hCGRP). Specification: 0.99 Molecular Formula: C38H47Br2N9O5.HCl Molecular Weight: 906.11 PubChem CID: 9919272 Isomeric SMILES: C1CN(CCC1N2CC3=CC=CC=C3NC2=O)C(=O)N[C@H](CC4=CC(=C(C(=C4)Br)O)Br)C(=O)N[C@@H](CCCCN)C(=O)N5CCN(CC5)C6=CC=NC=C6.Cl